A Phase II, Open-Label, Multicenter Trial to Investigate the Clinical Activity and Safety of Avelumab (MSB0010718C) in Subjects With Merkel Cell Carcinoma
Overview
- Phase
- Phase 2
- Intervention
- Avelumab
- Conditions
- Carcinoma, Merkel Cell
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Enrollment
- 204
- Locations
- 61
- Primary Endpoint
- Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
This is a multicenter, international, single-arm, open-label, Phase 2 trial to evaluate the efficacy and safety of avelumab in participants with metastatic Merkel cell carcinoma (MCC).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Signed written informed consent
- •Age 18 years and above
- •Histologically proven MCC
- •Participants must have received at least 1 line of chemotherapy for metastatic MCC and must have progressed after the most recent line of chemotherapy
- •For Part B - Participants must not have received any prior systemic treatment for metastatic MCC. Prior chemotherapy treatment in the adjuvant setting (no clinically detectable disease; no metastatic disease) is allowable if the end of treatment occurred at least 6 months prior to study start)
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Disease must be measurable with at least 1 uni-dimensional measurable lesion by RECIST Version 1.1 (including skin lesions)
- •Adequate hematological, hepatic and renal function (renal function considered adequate as per protocol definition)
- •Highly effective contraception for both male and female participants, if the risk of conception exists
- •Fresh Biopsy or Archival Tumor Tissue
Exclusion Criteria
- •Participation in another interventional clinical trial within the past 30 days (participation in observational studies is permitted)
- •Concurrent treatment with a non permitted drug
- •Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune checkpoints) such as antiprogrammed death 1 (PD-1), anti-PD-L1, or anticytotoxic T-lymphocyte antigen-4 (CTLA-4) antibody; for Part B, the Investigator must consult with the Medical Monitor and consider other co-regulatory targets such as 4-1BB
- •Concurrent anticancer treatment (for example, cytoreductive therapy, radiotherapy \[with the exception of palliative bone-directed radiotherapy, or radiotherapy administered on non-target superficial lesions\], immune therapy, or cytokine therapy except for erythropoietin). Radiotherapy administered to superficial lesions is not allowed if such lesions are considered target lesions in the efficacy evaluation or may influence the efficacy evaluation of the investigational agent
- •Major surgery for any reason, except diagnostic biopsy, within 4 weeks and/or if the participant has not fully recovered from the surgery within 4 weeks
- •Concurrent systemic therapy with steroids or other immunosuppressive agents, or use of any investigational drug within 28 days before the start of trial treatment. Short-term administration of systemic steroids (that is, for allergic reactions or the management of immune-related adverse events \[irAE\]) while on study is allowed. Also, participants requiring hormone replacement with corticosteroids for adrenal insufficiency are eligible if the steroids are administered only for the purpose of hormonal replacement and at doses \<= 10 mg or equivalent prednisone per day. Note: Participants receiving bisphosphonate or denosumab are eligible.
- •Participants with active central nervous system (CNS) metastases are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 2 months, and do not require continued steroid therapy
- •Previous malignant disease (other than MCC) within the last 5 years with the exception of basal or squamous cell carcinoma of the skin and for Part A cervical carcinoma in situ or for Part B carcinoma in situ (skin, bladder, cervical, colorectal, breast or low grade prostatic intraepithelial neoplasia or Grade 1 prostate cancer)
- •Prior organ transplantation, including allogeneic stem-cell transplantation
- •Part A: Known history of testing positive for HIV or known acquired immunodeficiency syndrome (AIDS) or any positive test for hepatitis B virus or hepatitis C virus indicating acute or chronic infection. For Part B, known history of testing positive for HIV or known AIDS in consultation with the Medical Monitor or HBV or HCV infection at screening (positive HBV surface antigen or HCV RNA if anti- HCV antibody screening test positive).
Arms & Interventions
Part A: Avelumab
Participants with metastatic Merkel cell carcinoma (MCC) after failing first-line chemotherapy received Avelumab at a dose of 10 milligram per kilogram (mg/kg) as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Intervention: Avelumab
Part B: Avelumab
Participants received Avelumab as first-line treatment for metastatic or distally recurrent MCC at a dose of 10 mg/kg as 1-hour intravenous infusion once every 2 weeks until therapeutic failure, significant clinical deterioration, unacceptable toxicity, or any criterion for withdrawal from the trial or investigational medicinal product occurs.
Intervention: Avelumab
Outcomes
Primary Outcomes
Part A: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time Frame: Up to 113 weeks
Confirmed BOR was determined according to RECIST 1.1and as adjudicated by an Independent Endpoint Review Committee(IERC) and defined as best response of any of complete response (CR), partial response(PR), stable disease(SD) and progressive disease(PD) recorded from date of randomization until disease progression/recurrence(taking smallest measurement recorded since start of treatment as reference). CR:Disappearance of all evidence of target/non-target lesions. PR:At least 30%reduction from baseline in sum of longest diameter(SLD) of all lesions. SD:Neither sufficient increase to qualify for PD nor sufficient shrinkage to qualify for PR. PD:at least a20% increase in SLD, taking as reference smallest SLD recorded from baseline/appearance of 1or more new lesions and unequivocal progression of non-target lesions. CR or PR must be confirmed by a subsequent tumor assessment preferably at next scheduled 6-weekly assessment, but no sooner than 5 weeks after initial documentation of CR or PR.
Part B: Durable Response Rate (DRR)
Time Frame: Up to 161 weeks
Durable response is defined as an objective response (confirmed complete response \[CR\] or confirmed Partial response \[PR\]) according to Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1, determined by the Independent Endpoint Review Committee (IERC), with a duration of at least 6 months. The DRR was determined as the percentage of participants with an objective response in terms of CR or PR according to RECIST 1.1, as determined by the IERC, with a duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions.
Secondary Outcomes
- Part A: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1(Up to 325 weeks)
- Part A: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1(Up to 325 weeks)
- Part A: Number of Participants With Treatment-Related (TR) Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Serious TEAEs and Treatment-Related TEAEs Leading to Death(Up to 325 weeks)
- Part A: Number of Participants With Clinically Significant Abnormalities in Laboratory Values Reported as Treatment Emergent Adverse Events (TEAEs)(Up to 325 weeks)
- Part A: Number of Participants With Clinically Significant Abnormalities in Vital Signs Reported as Treatment Emergent Adverse Events (TEAEs)(Up to 325 weeks)
- Part A: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG)(Up to 325 weeks)
- Part A: Interim Analysis: Overall Survival (OS) Time(Up to 87 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 3 Mar 2016))
- Part A: Final Analysis: Overall Survival (OS) Time(Time from first administration of trial treatment until death (Up to 325 weeks))
- Part B: Interim Analysis: Overall Survival (OS) Time(Up to 161 weeks (Data reported are per pre-specified interim analysis with a data cut-off date of 2 May 2019))
- Part A: Participant's Response Status According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 at 6 and 12 Months(At Month 6 and 12)
- Part A: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies(Up to 80 weeks)
- Part B: Final Analysis: Overall Survival (OS) Time(Time from first administration of trial treatment until death (Up to 396 weeks))
- Part A: Serum Concentration at End of Infusion (CEOI) of Avelumab(Day 1, 43, 85, 169, 253, 337 and 421)
- Part A: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb(Day 15, 29, 43, 57, 71, 85, 99, 169, 211, 253, 337 and 421)
- Part B: Number of Participants With Confirmed Best Overall Response (BOR) as Per Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1(Up to 396 weeks)
- Part B: Duration of Response According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1(Up to 396 weeks)
- Part B: Progression-Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1(Up to 396 weeks)
- Part B: Number of Participants With Treatment-Related (TR) Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Serious TEAEs and Treatment-Related TEAEs Leading to Death(Up to 396 weeks)
- Part B: Participant's Response Status According to RECIST 1.1 at 6 and 12 Months(At Month 6 and 12)
- Part B: Number of Participants With Positive Treatment Emergent Anti-Avelumab Antibodies(Up to 161 weeks)
- Part B: Serum Concentration at End of Infusion (CEOI) of Avelumab(At Day 1, 43 and 169)
- Part B: Minimum Serum Post-dose (Ctrough) Concentration of Aveluamb(Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505, Day 589, Day 673)